The herbicidal activity of various halogenated 4-phenoxy-phenoxy-propionic acids is well known in the art. For example, U.S. Pat. No. 3,954,442 specifically discloses the herbicidal utility of 2-[4-(2'-hydrogen or chloro-4'-chlorophenoxy)phenoxy]propionic acids and certain derivatives thereof. Similarly, U.S. Pat. Nos. 4,370,489 and 4,550,192 describe the even better herbicidal effect of 2-[4-(2'-chloro-4'-bromophenoxy)phenoxy]propionic acid and 2-[4-(2'-fluoro-4'-halophenoxy)phenoxy]propionic acids and their agriculturally acceptable derivatives, respectively.
Optical isomers are often known to have enhanced biological activity over the corresponding racemates. For example, U.S. Pat. No. 4,531,969 has demonstrated that the R-enantiomers of many 2-(4-phenoxyphenoxy)propionic acids are distinguished by a considerably enhanced herbicidal action compared with the racemates. Therefore, the application of mixtures enriched in the more efficacious R-enantiomer offers both economical and environmental advantages, since reduced quantities of herbicide are required to achieve comparable control.
Various methods for obtaining high concentrations of optical isomers are known. In addition to the resolution of a racemic mixture into its optically active components which, for example, depends on the conversion to diastereomers and subsequent physical separation, individual enantiomers can be obtained by direct synthesis employing an appropriate optically active starting material. For example, optically active 2-substituted propionic acids are conveniently prepared by the reaction of either an optically active 2-halopropionic acid or an optically active alkyl or aryl sulfonate of lactic acid with an appropriate nucleophile. Such nucleophilic displacement reactions generally occur with inversion of configuration of the asymmetric carbon atom of the starting material. Therefore, to prepare the R-enantiomer of the 2-substituted propionic acid, the S-enantiomer of the 2-halopropionic acid or sulfonate ester of lactic acid is employed as the starting material.
Theoretically, one can obtain essentially 100 percent of the desired enantiomer by this method. In practice, however, the optical purity of the final product is largely determined by (a) the optical purity of the starting material, (b) the nature of the leaving group, and (c) the specific conditions employed. Typically, one obtains products containing a ratio of from 70 to 90 percent of the desired enantiomer and, correspondingly, 10 to 30 percent of the other optical isomer. Such products are then said to possess an optical purity of 40 to 80 percent, i.e., from 40 to 80 percent of the mixture is the desired enantiomer and from 20 to 60 percent is a racemic mixture.
The importance of the nature of the leaving group in the starting propionic acid is illustrated in the article of G. Sakata et al. in J. Pesticide Sci., 10, 69-73 (1985). Product of the following optical purities were obtained with different leaving groups under comparable conditions: tosylate (.about.80 percent); mesylate (.about.45 percent); bromide (.about.45 percent); and chloride (.about.10 percent). Thus, although optically active 2-chloropropionic acid derivatives may be the most preferable starting material from the viewpoint of cost and availability, they are the least advantageous with respect to optical purity of the product.
Similarly, the importance of the reaction conditions is well known. For example, as shown in U.S. Pat. No. 4,532,328, the optical purity of the final product can be substantially enhanced by employing a 5 to 20 fold molar excess of the optically active starting material. Although enhanced optical yields are achieved, large amounts of relatively expensive optically active reagents such as S-methyl 2-chloropropionate must be recovered and recycled. Furthermore, this reagent may be susceptible to racemization under the reaction and recovery conditions thus precluding its direct recycle in the process.